醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig課件

1、醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigChapter 13 Design of medical research醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigChapter 13 Design of Medical Research (I) design 設(shè)計設(shè)計 research design 研究設(shè)計研究設(shè)計 reliable 可靠可靠 random error 隨機誤差隨機誤差 efficiency 效率效率 laboratory experiment 實驗

2、室實驗實驗室實驗 clinical trial 臨床試驗臨床試驗 medical survey 醫(yī)學(xué)調(diào)查醫(yī)學(xué)調(diào)查 control 對照、對照組對照、對照組 balance 均衡均衡 randomization 隨機化隨機化 replication 重復(fù)重復(fù) treatment 處理處理 subject 對象對象 effect 效應(yīng)效應(yīng) empty control 空白對照空白對照 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesigplacebo 安慰劑安慰劑 mutual control 互相對照互相對照 self control 自身對照自身對照 standard co

3、ntrol 標準對照標準對照 historical control 歷史對照歷史對照 homogeneity 均勻性均勻性 homogeneous 均勻的均勻的 prerequisite 前提條件前提條件 casual 隨意隨意 reproduce 重復(fù)重復(fù) pilot study 預(yù)試驗預(yù)試驗 blood sedimentation 血沉血沉 chemotherapy 化學(xué)療法化學(xué)療法 remission rate 緩解率緩解率 subject selection 對象選擇對象選擇 treatment assignment 處理安排處理安排 data collection 數(shù)據(jù)搜集數(shù)據(jù)搜集

4、validity 效度效度 reproducible 可重復(fù)可重復(fù) 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesiganimal experiment 動動物物實實驗驗 community intervention trial 社社區(qū)區(qū)干干預(yù)預(yù)試試驗驗 intervene 干干預(yù)預(yù) eligible subjects 合合格格對對象象 factor 因因素素 treatment factor 處處理理因因素素 non-treatment factors 非非處處理理因因素素 level 水水平平 objective 客客觀觀性性 accurate 準準確確 precis

5、e 精精確確 specific 特特異異的的 sensitive 敏敏感感的的 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig The aim of research design: l To get a reliable result in the lowest cost of manpower, time and money;l To estimate the random error within the observed data;l To promote the efficiency of the research There are two kinds o

6、f research: l Laboratory experiment and Clinical triall Medical survey醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig1. Control 2. Balance 3. Randomization 4. Replication 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig 1. ControllIf there is no control, then there is no comparison. OthersEffect of othersEffect of treatme

7、ntTreatmentSubjectOthersControlEffect of controlSubjectEffect of others醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglSome forms of control:(1) Empty control(2) Placebo control (for animal, Experimental control)(3) Mutual control(4) Self control(5) Standard control(6) Historical control醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesig

8、n；SurveydesigOthersEffect of othersEffect of treatmentTreatmentSubject AOthersSubject BEffect of others醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigOthersEffect of othersEffect of treatmentTreatmentSubject AOthers PlaceboEffect of placeboSubject BEffect of others醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigOthersEffe

9、ct of othersEffect of Treatment A Treatment I Subject AOthersTreatment II Effect ofTreatment B Subject BEffect of others醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigOthersEffect of othersEffect of treatmentTreatmentSubjectOthersControlEffect of controlSubjectEffect of others醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydes

10、igOthersEffect of othersEffect of treatmentTreatmentSubjectThere is no control group, but compare with certain “standard”醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigThere is no control group, but compare with “historical result”O(jiān)thersEffect of othersEffect of treatmentTreatmentSubject醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesig

11、n；Surveydesig 2. Balance: The experimental group and control group are almost the same in all aspects except the treatment. OthersEffect of othersEffect of treatmentTreatmentSubjectOthersControlEffect of controlSubjectEffect of others醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig 3. Randomization Many factors

12、, we know that they may influence the results, but they are very difficult to deal with Randomization is the best choice! Example To improve the homogeneity of subjects, collect a number of students with same age and gender; randomly arrange them into two groups to make them balance in height and we

13、ight. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglRandomization is the prerequisite of statistical inference.lRandomization CasuallRandomization means that all subjects in population have same probability to be sampled out for research. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig 4. ReplicationlOne meaning of rep

14、lication : The results can be reproduced in different labs and by different researchers.lAnother meaning of replication : The study should be performed in a big enough sample. Altman & Dore checked 90 papers: l39% mentioned their sample size and why.lSample sizes of 27% papers were too small to

15、make a conclusion.醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig How to estimate sample size in the design stage? Four parameters are needed: (1) : the maximal probability of type error is allowed(2) : the maximal probability of type I error is allowed(3) : the minimal difference between two means is allowed(

16、4) : the standard deviation among subjects in the same group醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig Check Table 13-2, or calculate byExample 13-1 A pilot study shows, the sample mean andstandard deviation of pulse among male patients with leadpoisoning are 67/min and 5.97/min respectively. To testwheth

17、er the population mean of this kind of patients islower than the mean of normal males (one-side test), howmany cases are needed? Given , take (Check Table 13-2, / 0.85, n=14)1. Comparison between the mean and a given number2)(uun10. 0,05. 097. 5, 567721321.12597. 5)282. 1645. 1 ()(22uun)or ,or (:,:0

18、00100HH醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigCheck Table 13-2, or calculate byExample 13-2 Comparing mean reductions of blood sedimentationbetween drug A and B. To test whether the effects of two drugs aredifferent (two-side), how many cases are needed? A pilot study shows, .Take , . (Check Table 13-3

19、, / 0.60, n=60) 211210:,:HH221)(2uunnmm/h98. 2 mm/h, 0 . 5 mm/h; 93. 1 mm/h, 2 . 32211SXSX98. 2, 8 . 12 . 30 . 510. 0,05. 0586 .578 . 198. 2)282. 196. 1 (2)(22221uunn醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig211210:,:HHCheck Table 13-4, or calculate byExample 13-3 Comparing two chemotherapies for lymphoma

20、, how many cases are needed? The pilot study shows, the remission rates are . Given . (Check Table 13-4, n=35) 221)(2uunn2 , )1 (,2121ppppppp%50%,1521pp10. 0,05. 0386 .3750. 015. 0)325. 01 (325. 0)282. 196. 1 (2)(22221uunn325. 02/ )50. 015. 0(p醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig Why? To plan and ar

21、range subject selection, treatmentassignment, data collection and statistical analysis To make sure validity, reproducible and economy. 2. Types of researchExperiment: animal experiment, clinical trial, community intervention trial Survey Both need well design ! 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigS

22、ubject: lSubject could be: gene, protein, cell, tissue, animal, patient or healthy population.(1)Subject should be clearly defined, and homogeneous. EligiblesubjectsTreatmenteffectsControl 3. Three elements of experimental design醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig2) Treatment: lA measure used to in

23、tervene a life process.lTreatment factor: drug Levels of treatment factor: dose A, dose B lTreatment factor and non-treatment factors should be identified. Non-treatment factors: age, gender, disease status, weather, environment lTreatment should be standardized:3) Effect: lChange caused by treatmen

24、t. lEffect measurement should be objective, accurate, precise, specific and sensitive.醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesigChapter 13 Design of Medical Research (II) completely random design 完全隨機設(shè)計完全隨機設(shè)計 randomly allocate 隨機安排隨機安排 independently sampling 獨立獨立抽樣抽樣 co

25、nfounding factors (confounder) 混雜因素混雜因素 paired design 配對設(shè)計配對設(shè)計 random block design 隨機區(qū)組設(shè)計隨機區(qū)組設(shè)計 block 區(qū)組區(qū)組 cross-over design 交叉設(shè)計交叉設(shè)計 wash-out period 清洗階段清洗階段 equity 公平公平 blinding (masking) 盲法盲法 single blinding 單盲單盲 double blinding 雙盲雙盲 psychological effect 心理效應(yīng)心理效應(yīng) effective components 有效成分有效成分 hea

26、lth condition survey 健康狀況調(diào)查健康狀況調(diào)查 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesigepidemiological survey 流流行行病病學(xué)學(xué)調(diào)調(diào)查查 etiologic survey 病病因因?qū)W學(xué)調(diào)調(diào)查查 clinical follow up survey 臨臨床床隨隨訪訪調(diào)調(diào)查查 sanitary survey 衛(wèi)衛(wèi)生生學(xué)學(xué)調(diào)調(diào)查查 questionnaire 問問卷卷 items 條條目目 coded 編編碼碼 interview 訪訪談?wù)?response rate 應(yīng)應(yīng)答答率率 overall survey (complet

27、e survey) 全全數(shù)數(shù)調(diào)調(diào)查查 national census 全全國國普普查查 sampling survey 抽抽樣樣調(diào)調(diào)查查 implementation 實實施施 simple random sampling 簡簡單單隨隨機機抽抽樣樣 systematic sampling 系系統(tǒng)統(tǒng)抽抽樣樣 ID code 身身份份證證號號碼碼 stratified sampling 分分層層抽抽樣樣 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesigstratum (pl. strata) 層層 cluster sampling 整群抽樣整群抽樣 typical surv

28、ey (case survey) 典型抽樣典型抽樣 characteristics 特征特征 case-control study 病例病例-對照研究對照研究 retrospective study 回顧性研究回顧性研究 rare diseases 罕見病罕見病 exposure 暴露暴露 outcome 結(jié)局結(jié)局 prospective study 前瞻性研究前瞻性研究 follow-up study 追蹤研究追蹤研究 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(1) Completely random designlRandomly allocate the

29、subjects into two or more groupslIndependently sampling from two or more populationsExample 13-4 Randomly allocate 10 animals into two groups. (Using Table 13-1, read 0-9 only) A: 1, 4, 6, 8, 9 B: 2, 3, 5, 7, 104.Commonly used experimental designs Animal 1 2 3 4 5 6 7 8 9 10 Random number* 1 2 0 3 8

30、 7 4 5 9 6 Group A B B A B A B A A B *From the 3rd line of Table 13-1 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglExample 13-5 Randomly allocate 15 animals into three groups. A: 4, 6, 8, 11, 15 B: 3, 5, 9, 12, 14 C: 1, 2, 7, 10, 13Data analysis: t test; rank sum testAdvantage: Simple; stableDisadvantage: I

31、f there are many confounders,they may not be balanced by randomization onlyAnimal 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Random number* 12 13 8 4 7 0 11 1 5 14 3 6 10 9 2 Group C C B A B A C A B C A B C B A *From the 21-th line of Table 13-1, omit 15-19 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(2) Paired de

32、signExample 13-6 Randomly allocate 8 pairs ofsubjects into two groups (read 0-7 only, odd for AB) A: 1-1, 2-2, 3-2, 4-1, 5-2, 6-1, 7-2, 8-1; B: the restlData analysis: Paired t test; signed rank sum testl Advantage: Well control the non-treatment factors, Save sample sizel Disadvantage: Difficult to

33、 perform in practice Used for short period studies Pair 1 2 3 4 5 6 7 8 Subject 1-1 1-2 2-1 2-2 3-1 3-2 4-1 4-2 5-1 5-2 6-1 6-2 7-1 7-2 8-1 8-2 Random number* 7 6 2 5 0 1 4 3 Group A B B A B A A B B A A B B A A B *From the 2nd line of Table 13-1, omit 8-19 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(3) Ran

34、dom block designExample 13-7 Four groups of subjects; fourtreatments: A, B, C, D.Block I II III IV Subject 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Random number* 1 4 3 2 1 2 4 3 2 1 4 3 3 2 4 1 Treatment A D C B A B D C B A D C C B D A *Read from line 4-7 of Table 13-1, where only random numbers 1-4

35、are kept. Design for Example 13-7 Treatment Block A B C D I 1 4 3 2 II 5 6 8 7 III 10 9 12 11 IV 16 14 13 15 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglData analysis: Analysis of variance for random block designlAdvantage: The individuals in same block are quite similar so that the comparison within block

36、 is more sensitive than that between completely randomized groups.lDisadvantage: if any one individual observation is missed, the data analysis in the block will be very difficult. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig 1st period wash-out 2nd periodGroup 1 A none BGroup 2 B none AExample 13-8 lIf the

37、re are 16 patients, then randomly allocate them into group 1 and 2 (same as Completely randomizeddesign).lIf there are 8 pairs of patients, then randomly allocate two subjects within each pair into group 1 and 2 (same as paired design).醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglData analysis: Analysis of

38、variance for cross-over designlAdvantage: Well control the non-treatment factors, save sample size; Everyone receives both treatments EquitylDisadvantage: Assume the subjects keep the same in 1st period and 2nd period - it can only be used for chronic diseases; Wash-out period is required the treatm

39、ent should be stopped during wash-out period 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglNecessary for clinical trial.lBlinding (Masking) - To reduce the bias caused by psychological effect of knowing the treatment Single blinding: Any patient does not know what treatment is taken. Double blinding: Both pa

40、tient and physician do not know the treatment.lPlacebo To ensure blinding Everything should be the same to the treatment group, except that it does not contain any effective components of the treatment. Special skills are needed for blinding and placebo. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig1. Survey

41、 Observe the existing process Without intervention Well designlExample for surveys: Health condition survey Epidemiological survey Etiologic survey Clinical follow up survey Sanitary survey .醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig (1) The purpose of survey, clear (2) The population concerned, well defi

42、ned. (3) Space, time and sample size, specified (4) Observed unit, well decided individual? Family? Class? (5) The questionnaire, well designedl Items, carefully chosen l Language, clear and specificl Possible answers, well coded in advance醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；SurveydesiglDirect observation Meas

43、urement, observation, test, count lInterview Form filling Group meeting Telephone or internet ( the response rate ?)醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(1) Overall survey (Complete survey) Example: National Census To get the population parameters directly There is no sampling error, but non-sampling

44、 error is relatively high (2) Sampling survey Sampling Observation Statistical inference knowledge about population Advantage: Efficient Disadvantage: Complicate in design, implementation and analysis 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig Simple random samplinglEvery individual has same probability t

45、o be sampled.lSuitable for small population. Systematic samplinglAccording to the sequence of individuals, to sample subjects in a fixed interval.lWhen population has a sequence number ( such as ID code), it is convenient to carry out. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig Stratified samplinglThe pop

46、ulation is stratified according some factors that may influence the results of study and then the individuals in strata were randomly sampled.lSome important confounding factors could be controlled by stratified sampling. Cluster samplinglIf the individuals belong to certain unit ( such as community

47、, school, class, city, county), we may directly sample the unit other than individuals. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig Stratified sampling Systematic sampling Simple random sampling Cluster sampling醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(3) Typical survey (case survey) Advantage: Only a few typic

48、al subjects are observed, who well reflect the main characteristics of same kind of subjects. Disadvantage: There is no ground for any statistical inference. 醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(4) Case-control survey (retrospective study) Good for rare diseases: Outcome Exposure (Cause?) “Case”: Patients “Control”: Non patients, main confounders are similar to the patients Comparing the frequency (or intensity) of exposure 1:1 case-control; 1:m case-control group group case control醫(yī)學(xué)統(tǒng)計學(xué)10.Experimentdesign；Surveydesig(5) Cohort survey (Follow-up s